Acne vulgaris is one of the most common diseases of the skin and in cases of extreme disfigurement can sometimes have severe consequences for the personality development of young people with ensuing social and economic problems. Adolescents suffering from acne show higher levels of anxiety, greater social inhibition and increased aggression compared to non-acne individuals. Amongst skin diseases, acne is the second highest cause of suicides.
Acne is an exclusively human disease and a unique condition of human sebaceous follicles of the face, chest and back. Spontaneous regression is common, taking about 15 years to complete. However, in about 5 percent of cases, acne persists beyond the age of 25 years and extends into the fourth and fifth decades of life. The earlier the symptoms start, the more severe is the course of the disease. The prevalence of the disease does not reflect any preference for male or female but usually the course is more severe in males.
The onset of the disease in an individual coincides with entry into puberty and is associated with an androgen-driven rise in sebum excretion rate and an increased colonisation of the sebaceous follicles with Propionibacterium acnes (P. acnes). Recent data indicates that the initiation of individual lesions is primarily inflammatory rather than via keratinocyte hyperproliferation.
Contrary to popular opinion, hygiene and diet have little or no effect on the aetiology of acne. Acne can be exacerbated by external factors such as friction (acne mechanica) (Shalita A R (1983) Cosmetics and Toiletries 98: 57-60) and pore-clogging cosmetics (acne cosmetica) (Mills O. H. & Kilgman A. M. (1988) Dermatol. Clin. 1: 365-370). The bacterium P. acnes is an inhabitant of the human skin and forms a major part of the natural skin flora. There is a wealth of circumstantial evidence implicating P. acnes as a major factor in the disease: increased colonisation of the skin by P. acnes is associated with the onset of the disease; patients with severe acne are significantly more sensitised to P. acnes than normal individuals; the overall immunological status of patients is elevated compared to acne-free individuals of the same age; successful antibiotic treatment reduces the density of P. acnes on the skin; and antibiotic therapeutic failure is associated with the presence of antibiotic resistant P. acnes on the skin of the patient.
Current treatments for acne focus on various factors contributing to the disease. In summary, anti-comedonal treatments include retinoids and azelaic acid (topical treatments) and isotretinoin (oral treatments); anti-P. acnes treatments include benzoyl peroxide, azelaic acid, erythromycin, tetracycline and clindamycin (topical treatments) and tetracycline, erythromycin, minocycline and trimethoprim (oral treatments); anti-inflammatory treatments include tetracycline, erythromycin, clindamycin and nicotinamide (topical treatments) and tetracycline, minocycline, trimethoprim and isotretinoin (oral treatments); and anti-seborrhoeic treatments include spironolactone (topical treatments) and Dianette™ and isotretinoin (oral treatments).
The more common mild and moderate cases of acne are treated with antibiotics, usually topically. There are increasing concerns emerging over the use of antibiotics for acne, where treatments last for long periods of time, up to 2-3 years in some cases. The concerns are two fold. First, the emergence of antibiotic resistant P. acnes world-wide with the consequence of reducing their efficacy for acne therapy. Second and possibly more importantly, there is the selection of an increasing pool of antibiotic resistant genes in the commensal microflora, mainly coagulase-negative staphylococci and corynebacteria, on patients' skin. These resistance genes may be horizontally transferred to related species, e.g. Staphylococcus aureus, which is a major opportunistic pathogen in the hospital and community environments. Therefore all efforts are required to restrict the use of antibiotics over extended treatment periods as used in the treatment of acne. Obtaining licences to market antibiotic therapies for acne is becoming especially difficult.
Side effects from these treatments are commonplace. Mild irritant dermatitis is associated with virtually all topical therapies (Cunliffe W. J., (2001) Pharmaceut. J. 267 749-752). Oral courses of antibiotics have side effects regardless of the condition for which they are prescribed and these often result from their lack of specificity, unbalancing (in due course) much of the bacterial flora in many sites in the body. This leaves room for resistant flora to flourish, resulting in, for example, vaginal candidiasis in women. Retinoid treatment has many side effects: it is a teratogen; causes cheilitis, facial dermatitis and conjunctivitis; leads to secondary skin infections; and has been associated with mood swings and depression.
Therefore, there is a need to develop new approaches for acne therapy which specifically target P. acnes. 
The idea of employing bacteriophage (naturally occurring bacterial viruses) for the treatment or prevention of bacterial diseases was realised relatively soon after the discovery of phage (the words “bacteriophage” and “phage” are used interchangeably throughout this specification) by Felix d'Herelle in 1917. The fact that bacteriophage can specifically infect a bacterial host and rapidly kill it suggested to d'Herelle that this was potentially a very effective way of controlling bacterial infection in man (for review, see “Felix d'Herelle and the Origins of Molecular Biology” William C. Summers (Yale University Press, ISBN 0-300-07127-2)). This potential was never fully realised because of the advent of the antibiotic era, but phage therapy has been pursued since then, in many cases successfully, in former states of the USSR and Eastern Europe.
The emergence of drug resistance and the difficulty in developing novel antibiotics and vaccines has highlighted a growing need to find alternative methods of treatment.
WO03/080823 discloses a method for generating candidate bacteriophage for use in therapy by mutating temperate bacteriophage and producing a cocktail of phages. This disclosure specifically selects lysogenic phage, observing that for some bacteria they are more numerous and, therefore, easier to isolate than lytic phage. The phage then have to be mutated to produce lytic vir mutants, in order to avoid the problems associated with lysogenic phage as a therapy, as discussed further below. Treatment of P. acnes is mentioned.
EPO414304 relates to the use of bacteriophage to kill bacteria, including P. acnes. There is no disclosure of a bacteriophage capable of lysing multiple strains of P. acnes bacteria and yet which is incapable of lysing a bacterium which is not P. acnes and incapable of sustaining lysogeny in a bacterium.
Jong et al (Med. Microbiol. Immunol. 161 (1975) 263-271) describes isolation of P. acnes phage. The paper focuses on the classification of the phage and does not disclose a bacteriophage capable of lysing multiple strains of P. acnes bacteria and yet which is incapable of lysing a bacterium which is not P. acnes and incapable of sustaining lysogeny in a bacterium.
Puhvel & Reisner (Amer. Soc. Microbiol. 72 (1972) V201) is an abstract relating to the generation of lysogenic phage-resistant strains of P. acnes. 
WO01/51066 relates to the use of bacteriophage to reduce risk of infection or sepsis, particularly in immunocompromised patients. The disclosed methodology aims to achieve the numerical reduction or elimination of various members of the body's natural bacterial flora, in order to reduce the chance of them causing disease in immunocompromised patients. This is specifically risk reduction rather than cure and is concerned in particular with infections which complicate conditions such as certain cancers, AIDS and cystic fibrosis and which complicate the condition of transplant patients. No mention is made of treatment of P. acnes. 
U.S. Pat. No. 6,121,036 relates to a purified, host specific, non-toxic, wide host range bacteriophage preparation containing at least two phage. The document describes some of the features of an effective phage therapy—that it should be safe, have broad host range and kill a large proportion of bacteria strains—and indicates that such a preparation of appropriate phage could be used to treat P. acnes infections. However, no disclosure is made about which phage are suitable for this purpose or that such safe, lytic, broad host range phage exist for P. acnes. 
WO02/07742 purports to disclose a method for potentiating a wider host range for a phage by cloning tail protein-encoding genes from another phage with different host specificity. The document indicates that wide specificity is desirable from a phage therapy point of view but, rather than selecting from naturally occurring phage variants, describes the synthetic construction of a hybrid bacteriophage with dual tail fibre types, therefore having corresponding dual host specificity. This specificity is hypothetically extended to apply the invention in the engineering of a phage which can infect not only different species strains but different bacteria within a species and even within different genera. However, there is no evidence for this potential beyond results showing that a hybrid phage had been created having the ability to infect two different strains of Escherichia coli. The application of a suitably modified phage for gene therapy in humans is also contemplated. Specific phage, modified or unmodified, for the treatment of acne are not disclosed. There is no mention of a P. acnes bacteriophage with a single host species specificity but with multiple strain specificity.
US2005/0032036 describes a method for sorting through a phage collection and determining the composition of a phage cocktail in order to optimise broad host range infection and lysis, particularly in reference to Pseudomonas and Staphylococcus strains. No disclosures are made in relation to the field of acne phage therapy.
WO2005/009451 relates in particular to the use of bacteriophage as a part of a combination therapy with traditional, chemical antibiotics, particularly in the treatment of Pseudomonas aeruginosa infections and particularly in the treatment of bacteria within biofilms. It describes the difficulty in finding phage with sufficiently broad host specificity to be of therapeutic value for treatment of any given infection and advocates the use of multiple bacteriophage types for therapy, whether simultaneously, separately or sequentially. It also indicates that greater virulence in a phage can be induced artificially by genetic manipulation methods to produce phage with broader specificity or greater infection potential. There is no mention of P. acnes, which is not characterised by biofilm formation.
US2004/0241825 discloses several methods for genetically labelling bacteriophage (with a non-functional stretch of DNA that can be detected by, for example, PCR, enabling identification of the phage), identifying non-cross reacting bacteriophage (a multi-step process to isolate phage against the target host and, from these, isolating bacteriophage which do not infect more than 5% of non-pathogenic, non-target hosts) and, finally, a method for selecting phage that are resistant to genetic modification by host bacteria (which involves infecting bacteria with a sample of bacteriophage, isolating progeny phage and comparing the restriction digest patterns of the original bacteriophage and the progeny to identify any differences that would be indicative of genetic modification). Implicit in this disclosure is the difficulty in identifying suitable candidate bacteriophage for use in a therapy. The application of this methodology to P. acnes is not described.
Several conference presentations by the research group of Michael Davis at Central Connecticut State University have outlined plans to identify lytic phage having broad host range specificity (Vieira T. and Davis M. A. (1999) Viruses as Therapeutic Agents for Treating Bacterial Infections. Poster presentation on Apr. 24, 1999 at the 53rd Annual Eastern Colleges Science Conference, Sacred Heart University, Fairfield Conn.; Jedrzkiewicz B. and Davis M. A. (2000) Combating the Antibiotic Resistance Crisis: Therapeutic Use of Bacteriophages (Viruses) for Treating Acne, A Bacterial Disease. Poster presentation on Apr. 1, 2000 at the 54th Annual Eastern Colleges Science Conference, Wagner College, Staten Island N.Y.; Hany C. et al., (2001) The Use of Bacteriophage to Treat Acne, A Bacterial Disease. Poster presentation on Mar. 31, 2001 at the 55th Annual Eastern Colleges Science Conference, Wilkes University, Wilkes-Barre Pa.; Armack S. et al. (2002) Bacteriophage Therapy For The Treatment Of The Bacterial Disease Acne. Poster presentation on Apr. 27, 2002 at the 56th Annual Eastern Colleges Science Conference, Niagara University, Niagara N.Y.; Aminti K. et al. (2003) Bacteriophage Therapy For The Disease Acne: Identification And Purification Of Candidate Bacteriophage. Poster presentation on Apr. 12, 2003 at the 57th Annual Eastern Colleges Science Conference, Ithaca College, Ithaca N.Y.; Geronimo J. et al (2004) Bacteriophage Therapy For the Skin Disease Acne. Poster presentation on Apr. 2, 2004 at the 58th Annual Eastern Colleges Science Conference, Manhattan College, Riverdale N.Y.). No disclosures have been made in relation to the specific properties of such phage or to specific phage isolates.